A recent study published analyzed circulating biomarkers of systemic inflammation and neuroinflammation in patients with long COVID (LC).
Study
In the present study, researchers analyzed circulating biomarkers of neuroinflammation and systemic inflammation in LC patients. This case-control study was conducted in a Norwegian hospital between January 1, 2022, and April 1, 2024. Eligible participants, aged 16–80 years, had confirmed SARS-CoV-2 infection. LC cases met the National Institute for Health and Care Excellence (NICE) criteria for LC, i.e., persistent symptoms for > 12 weeks, unexplained by an alternative diagnosis.
Controls were individuals who completely recovered from SARS-CoV-2 infection and did not have persisting symptoms. Individuals with chronic inflammatory diseases, autoimmune diseases, anemia, hypothyroidism, cancer, and untreated comorbidities affecting fatigue, and those using systemic corticosteroids were excluded. Routine biochemical and hematological tests, including CRP, were performed at the hospital.
Proinflammatory cytokines, i.e., interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α), were measured using the MSD S-Plex electrochemiluminescence immunoassay platform. In addition, glial fibrillary acidic protein (GFAP, a neuroinflammation biomarker), neurofilament light (NfL, a biomarker of neuronal damage), triggering receptor expressed on myeloid cells 2 (TREM2), CRP, IL-6, IL-1β, and TNF-α were measured using the ultrasensitive nucleic acid-linked immuno-sandwich assay (NULISA).
Results
The study recruited 112 individuals, of these, 96 were included in the final analytic sample. They were aged 46.7 years, on average. Most participants were female (85.4%), and the median time since COVID-19 diagnosis was 69 weeks. LC cases and recovered controls were well-matched for sex, age, and the time since COVID-19.
CRP measured in routine hospital analyses was not significantly different between cases and controls. TNF-α and IL-6 levels were marginally elevated in LC cases relative to recovered controls. NULISA revealed nominally (in unadjusted analyses) increased levels of inflammatory markers (CRP, TREM2, TNF-α, and IL-6) in LC cases than in controls. In contrast, GFAP and NfL did not significantly differ between groups.
After false discovery rate (FDR) correction, inflammatory biomarkers were no longer significantly different between LC cases and controls, suggesting that any differences were either absent or too subtle to be detected reliably in this cohort. Finally, Spearman correlation analyses revealed no correlation between inflammatory biomarkers and symptom severity, suggesting that these biomarker levels did not predict symptom burden in the cohort.
Conclusion
Taken together, the study found no significant differences in neurological and inflammatory biomarkers between LC cases and recovered controls at 69 weeks after SARS-CoV-2 infection. These results do not support evidence of overt immune activation, inflammation, or neuronal injury in the studied cohort at this late stage of infection. This discrepancy with earlier studies may reflect differences in follow-up duration, as the longer follow-up in this study may have allowed sufficient time for the resolution of acute inflammation and viral clearance.
One reason prior studies have found ongoing immune activation and inflammation in LC is that their cohorts included people with preexisting chronic inflammatory or autoimmune conditions, which show many of the same inflammatory markers and clinical symptoms as those in LC. The current cohort was designed to minimize potential confounding from such conditions and, therefore, better isolate LC-related biological signals.
The study’s limitations include its small sample size, cross-sectional design that precludes causal inference, use of a select biomarker panel that may mean other inflammatory pathways are active, and reliance on blood-based biomarkers with no paired cerebrospinal fluid or neuroimaging data, as well as the use of assay outputs reported in normalized protein expression units rather than absolute concentrations, which may limit comparisons with external reference values.
Overall, the findings do not support persistent systemic inflammation, neuroinflammation, or neuronal injury detectable in blood at this stage of long COVID, though the authors note that extremely low-level immune activation, potentially below current biomarker detection thresholds, or other mechanisms could still contribute to symptoms and warrant further investigation in larger cohorts.
Source:
https://www.news-medical.net/news/20260304/Nearly-70-weeks-after-infection-long-COVID-patients-show-no-detectable-inflammation-in-blood-tests.aspx